Measuring Metacognition in Cancer: Validation of the Metacognitions Questionnaire 30 (MCQ-30)

Objective The Metacognitions Questionnaire 30 assesses metacognitive beliefs and processes which are central to the metacognitive model of emotional disorder. As recent studies have begun to explore the utility of this model for understanding emotional distress after cancer diagnosis, it is important also to assess the validity of the Metacognitions Questionnaire 30 for use in cancer populations. Methods 229 patients with primary breast or prostate cancer completed the Metacognitions Questionnaire 30 and the Hospital Anxiety and Depression Scale pre-treatment and again 12 months later. The structure and validity of the Metacognitions Questionnaire 30 were assessed using factor analyses and structural equation modelling. Results Confirmatory and exploratory factor analyses provided evidence supporting the validity of the previously published 5-factor structure of the Metacognitions Questionnaire 30. Specifically, both pre-treatment and 12 months later, this solution provided the best fit to the data and all items loaded on their expected factors. Structural equation modelling indicated that two dimensions of metacognition (positive and negative beliefs about worry) were significantly associated with anxiety and depression as predicted, providing further evidence of validity. Conclusions These findings provide initial evidence that the Metacognitions Questionnaire 30 is a valid measure for use in cancer populations

A randomised feasibility study of serial magnetic resonance imaging to reduce treatment times in Charcot neuroarthropathy in people with diabetes (CADOM): A protocol

Background Charcot neuroarthropathy is a complication of peripheral neuropathy associated with diabetes which most frequently affects the lower limb. It can cause fractures and dislocations within the foot, which may progress to deformity and ulceration. Recommended treatment is immobilisation and offloading, with a below knee non-removable cast or boot. Duration of treatment varies from six months to more than one year. Small observational studies suggest that repeated assessment with Magnetic Resonance Imaging improves decision making about when to stop treatment, but this has not been tested in clinical trials. This study aims to explore the feasibility of using serial Magnetic Resonance Imaging without contrast in the monitoring of Charcot neuroarthropathy to reduce duration of immobilisation of the foot. A nested qualitative study aims to explore participants’ lived experience of Charcot neuroarthropathy and of taking part in the feasibility study. Methods We will undertake a two arm, open study, and randomise 60 people with a suspected or confirmed diagnosis of Charcot neuroarthropathy from five NHS, secondary care multidisciplinary Diabetic Foot Clinics across England. Participants will be randomised 1:1 to receive Magnetic Resonance Imaging at baseline and remission up to 12 months, with repeated foot temperature measurements and x-rays (standard care plus), or standard care plus with additional three-monthly Magnetic Resonance Imaging until remission up to 12 months (intervention). Time to confirmed remission of Charcot neuroarthropathy with off-loading treatment (days) and its variance will be used to inform sample size in a full-scale trial. We will look for opportunities to improve the protocols for monitoring techniques and the clinical, patient centred, and health economic measures used in a future study. For the nested qualitative study, we will invite a purposive sample of 10-14 people able to offer maximally varying experiences from the feasibility study to take part in semi-structured interviews to be analysed using thematic analysis. Discussion The study will inform the decision whether to proceed to a full-scale trial. It will also allow deeper understanding of the lived experience of Charcot neuroarthropathy, and factors that contribute to engagement in management and contribute to the development of more effective patient centred strategies. Trial registration ISRCTN, ISRCTN, 74101606. Registered on 6 November 2017, http://www.isrctn.com/ISRCTN74101606?q=CADom&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-searc

Persistent urinary incontinence and delivery mode history: a six-year longitudinal study.

Objective: To investigate the prevalence of persistent and long term postpartum urinary incontinence and associations with mode of first and subsequent delivery. Setting: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). Design: Longitudinal study Population: 4214 women who returned postal questionnaires 3 months and 6 years after the index birth. Methods: Symptom data were obtained from both questionnaires and obstetric data from case-notes for the index birth and the second questionnaire for subsequent births. Logistic regression investigated the independent effects of mode of first delivery and delivery mode history. Main outcome measures: Urinary incontinence – persistent (at 3 months and 6 years after index birth) and long-term (at 6 years after index birth). Results: The prevalence of persistent urinary incontinence was 24%. Delivering exclusively by Caesarean section was associated with both less persistent (OR= 0.46, 95% CI 0.32 to 0.68) and long term urinary incontinence (OR=0.50, 95% CI 0.40 to 0.63). Caesarean section birth in addition to vaginal delivery however was not associated with significantly less persistent incontinence (OR 0.93, 95%CI 0.67 to 1.29). There were no significant associations between persistent or long-term urinary incontinence and forceps or vacuum extraction delivery. Other significantly associated factors were increasing number of births and older maternal age. Conclusions: The risk of persistent and long term urinary incontinence is significantly lower following Caesarean section deliveries but not if there is another vaginal birth. Even when delivering exclusively by Caesarean section, the prevalence of persistent symptoms (14%) is still high

Facilitating return to work through early specialist health-based interventions (FRESH): protocol for a feasibility randomised controlled trial

Background Over one million people sustain traumatic brain injury each year in the UK and more than 10 % of these are moderate or severe injuries, resulting in cognitive and psychological problems that affect the ability to work. Returning to work is a primary rehabilitation goal but fewer than half of traumatic brain injury survivors achieve this. Work is a recognised health service outcome, yet UK service provision varies widely and there is little robust evidence to inform rehabilitation practice. A single-centre cohort comparison suggested better work outcomes may be achieved through early occupational therapy targeted at job retention. This study aims to determine whether this intervention can be delivered in three new trauma centres and to conduct a feasibility, randomised controlled trial to determine whether its effects and cost effectiveness can be measured to inform a definitive trial. Methods/design Mixed methods study, including feasibility randomised controlled trial, embedded qualitative studies and feasibility economic evaluation will recruit 102 people with traumatic brain injury and their nominated carers from three English UK National Health Service (NHS) trauma centres. Participants will be randomised to receive either usual NHS rehabilitation or usual rehabilitation plus early specialist traumatic brain injury vocational rehabilitation delivered by an occupational therapist. The primary objective is to assess the feasibility of conducting a definitive trial; secondary objectives include measurement of protocol integrity (inclusion/exclusion criteria, intervention adherence, reasons for non-adherence) recruitment rate, the proportion of eligible patients recruited, reasons for non-recruitment, spectrum of TBI severity, proportion of and reasons for loss to follow-up, completeness of data collection, gains in face-to-face Vs postal data collection and the most appropriate methods of measuring primary outcomes (return to work, retention) to determine the sample size for a larger trial. Discussion To our knowledge, this is the first feasibility randomised controlled trial of a vocational rehabilitation health intervention specific to traumatic brain injury. The results will inform the design of a definitive trial

Cultural differences in postnatal quality of life among German-speaking women - a prospective survey in two countries.

Assessment of quality of life after childbirth is an important health-outcome measurement for new mothers and is of special interest in midwifery. The Mother-Generated Index (MGI) is a validated instrument to assess postnatal quality of life. The tool has not been applied for making a cross-cultural comparison before. This study investigated (a) responses to the MGI in German-speaking women in Germany and Switzerland; and (b) associations between MGI scores on the one hand and maternity and midwifery care on the other

A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer

Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer

Fatigue Intervention by Nurses Evaluation - The FINE Trial. A randomised controlled trial of nurse led self-help treatment for patients in primary care with chronic fatigue syndrome: study protocol. [ISRCTN74156610]

Background: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis and serious personal and economic consequences. Evidence for the effectiveness of any treatment for CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to be successful in improving fatigue and physical functioning in patients in secondary care. The treatment involves providing patients with a readily understandable explanation of their symptoms, from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic rehabilitation when delivered by specially trained general nurses in primary care. We selected a client-centred counselling intervention, called supportive listening, as a comparison treatment. Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in primary care, is more readily available, and controls for supportive therapist contact time. Our control condition is treatment as usual by the general practitioner (GP). Methods and design: This study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried out alongside the clinical trial. Three adult general nurses were trained over a six month period to deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs' drivers and barriers towards referral

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Melanoma cells break down LPA to establish local gradients that drive chemotactic dispersal.

The high mortality of melanoma is caused by rapid spread of cancer cells, which occurs unusually early in tumour evolution. Unlike most solid tumours, thickness rather than cytological markers or differentiation is the best guide to metastatic potential. Multiple stimuli that drive melanoma cell migration have been described, but it is not clear which are responsible for invasion, nor if chemotactic gradients exist in real tumours. In a chamber-based assay for melanoma dispersal, we find that cells migrate efficiently away from one another, even in initially homogeneous medium. This dispersal is driven by positive chemotaxis rather than chemorepulsion or contact inhibition. The principal chemoattractant, unexpectedly active across all tumour stages, is the lipid agonist lysophosphatidic acid (LPA) acting through the LPA receptor LPAR1. LPA induces chemotaxis of remarkable accuracy, and is both necessary and sufficient for chemotaxis and invasion in 2-D and 3-D assays. Growth factors, often described as tumour attractants, cause negligible chemotaxis themselves, but potentiate chemotaxis to LPA. Cells rapidly break down LPA present at substantial levels in culture medium and normal skin to generate outward-facing gradients. We measure LPA gradients across the margins of melanomas in vivo, confirming the physiological importance of our results. We conclude that LPA chemotaxis provides a strong drive for melanoma cells to invade outwards. Cells create their own gradients by acting as a sink, breaking down locally present LPA, and thus forming a gradient that is low in the tumour and high in the surrounding areas. The key step is not acquisition of sensitivity to the chemoattractant, but rather the tumour growing to break down enough LPA to form a gradient. Thus the stimulus that drives cell dispersal is not the presence of LPA itself, but the self-generated, outward-directed gradient